Since the founding of CURE by Dr. Morton I. Grosssman in 1973, a strong tradition of expertise has existed for exploring the physiological mechanisms involved in the regulation of GI function under normal and pathological conditions, as recently reviewed by the Animal Models Core Co-Director (1). In the past two decades, tremendous increases in knowledge derived from cell and molecular biological approaches have driven interest to evaluate in vitro findings within the context of integrative physiological models. Conversely, observations derived from the role of specific endogenous hormones or transmitters in the regulation of normal or abnormal GI functions in in vivo models have provided the impetus for focused mechanistic evaluation at the cellular level using molecular biological methods. Indeed, a common theme in many of the research programs of the Center investigators is the elucidation of the pathophysiological role and molecular mechanism of action of gastrointestinal peptide hormones, neuropeptides, paracrine regulators and classical neurotransmitters. Thus, in vivo studies are important for the implementation of many research programs of CURE: DDRCC members to: 1. Assess the biological significance of mechanisms elucidated in vitro; 2. Dissect the neural, hormonal and paracrine mechanisms involved in integrated physiological regulation of GI function; 3. Test biological activity of new reagents (i.e., antibodies, selective receptor agonists or antagonists or novel peptides); 4. Establish relevant models of GI diseases.